BRD4 inhibition for the treatment of pathological organ fibrosis [version 1; referees: 2 approved]

Abstract

Fibrosis is defined as excess deposition of extracellular matrix, resulting in tissue scarring and organ dysfunction. It is estimated that 45% of deaths in the developed world are due to fibrosis-induced organ failure. Despite the well-accepted role of fibrosis in the pathogenesis of numerous diseases, there are only two US Food and Drug Administration–approved anti-fibrotic therapies, both of which are currently restricted to the treatment of pulmonary fibrosis. Thus, organ fibrosis represents a massive unmet medical need. Here, we review recent findings suggesting that an epigenetic regulatory protein, BRD4, is a nodal effector of organ fibrosis, and we highlight the potential of small-molecule BRD4 inhibitors for the treatment of diverse fibrotic diseases.

Keywords

• Cell Signaling
• Control of Gene Expression
• Extrapulmonary Disorders & Therapeutic Interventions
• Gastrointestinal Pharmacology
• Immunopharmacology & Hematologic Pharmacology
• Interstitial Lung Diseases
• Liver Biology & Pathobiology
• Liver Failure & Liver Disease
• Nuclear Structure & Function
• Pathophysiology of Chronic Kidney Disease (CKD)
• Renal Immunology & Pathology (incl. Glomerular Diseases)
• Renal Pharmacology
• Respiratory Pharmacology